The present invention relates to controlled release unit dose formulations of pharmaceuticals. In the prior art, many techniques have been used to provide controlled and extended-release pharmaceutical dosage forms in order to maintain therapeutic serum levels of medicaments and to minimize the effects of missed doses of drugs caused by a lack of patient compliance.
In the prior art, extended release tablets containing osmotic tablets have been described and manufactured which have had an osmotically active drug core surrounded by a semipermeable membrane. The core is divided into two layers (compositions) one of which contains the active drug and the other contains a push layer of pharmacologically inactive ingredients which are osmotically active in the presence of gastrointestinal fluids. An outer water impermeable coating covers the tablet which is provided with an aperture that is formed by laser drilling an orifice to allow the drug to be pushed out of the tablet. A product of this type is disclosed in U.S. Pat. Nos. 4,783,337; 4,765,989; 4,612,008; and 4,327,725 and is sold commercially as Procardia XL(copyright). Other controlled release compositions include those described in U.S. Pat. Nos. 3,948,254 and 4,036,227.
The osmotic dosage forms that are disclosed in U.S. Pat. No. 4,783,337 are described as having a passageway which includes an aperture, orifice, hole, porous element, hollow fiber, capillary tube, microporous insert, pore, microporous overlay or bore which extends through the semipermeable lamina wall into a drug layer. The patent also states that the passageway may be formed by mechanical drilling, laser drilling, eroding and erodible element, extracting, dissolving, bursting or leaching a passageway-former from the wall of the osmotic dosage form (col. 14, line 35 et seq.) which are pre-formed in the tablet during the manufacturing process. The only exemplified technique of forming a passageway in U.S. Pat. No. 4,783,337 is the use of a laser to drill a hole in the outer layer of the tablet and the dosage forms are all based on a drug layer superimposed on a secondary layer.
U.S. Pat. No. 4,285,987 described an osmotic tablet which had a laser drilled aperture into the core of the tablet. The laser drilled hole was plugged with leachable sorbitol which was leached out in the presence of gastrointestinal fluid.
U.S. Pat. No. 4,503,030 discloses an osmotic device for delivering drugs to the stomach and the intestine. This device has a shaped wall placed around a compartment which is described as a compartment which maintains its physical and chemical integrity in the stomach but loses its chemical and physical integrity in the intestine. U.S. Pat. No. 4,587,117 describes an oral osmotic device which has a shaped wall which loses its integrity at a pH of 3.5 to 8.0, a compartment and a passageway from the compartment to the exterior of the medical device.
The present invention is concerned with providing an osmotic tablet for highly water insoluble medicaments that avoids the need to have a separate xe2x80x9cpushxe2x80x9d layer in the core which contains no medicament and which avoids the need to have a pre-formed passageway in the tablet to allow the drug to be pushed out of the core.
The present invention is directed to a controlled release dosage form which comprises:
(a) a homogeneous compressed core which comprises:
(i) a medicament which is very slightly soluble to practically insoluble in water at 25xc2x0 C.;
(ii) a water soluble osmotic compound
(iii) one or more osmotic polymers; and
(b) a membrane coating which completely covers said core tablet which comprises a mixture of a:
(i) a water insoluble pharmaceutically acceptable polymer; and
(ii) a pH dependent polymer such as an enteric coating polymer, the weight ratio of the pH dependent polymer to the water insoluble pharmaceutically acceptable polymer being 0.1:1 to 0.75:1.
It is a primary object of the invention to provide a controlled release pharmaceutical tablet which has an osmotic core covered with an external polymer membrane that provides therapeutic blood levels of a medicament with once a day administration.
It is also an object of the invention to provide an osmotic tablet which has a homogeneous core composition.
It is also an object of the present invention to provide a controlled release pharmaceutical tablet that has a homogeneous osmotic core and no pre-formed aperture in the external polymeric membrane.
It is also an object of this invention to provide a controlled release pharmaceutical tablet having only a homogeneous osmotic core wherein the osmotic core component may be made using ordinary tablet compression techniques.
These and other objects of the invention will become apparent from the appended specification.